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Developmental and Anatomical Patterns Of IL-2 Gene Expression in Vivo in The Murine Thymus

Yang-Snyder, Julia A. and Rothenberg, Ellen V. (1993) Developmental and Anatomical Patterns Of IL-2 Gene Expression in Vivo in The Murine Thymus. Developmental Immunology, 3 (2). pp. 85-102. ISSN 1044-6672. PMCID PMC2275923.

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Interleukin-2 (IL-2) is a potent growth factor that mature T lymphocytes synthesize and use as a proliferation signal. Much controversy has arisen concerning whether it is used to drive the extensive proliferation of immature pre-T cells in the thymus. Immature thymocytes acquire the competence to express IL-2 at an early stage, but it has remained uncertain whether they are activated to exercise this competence in vivo. Therefore, we have used in situ hybridization and immunohistochemistry on serial sections obtained from fetal and adult thymuses of normal C57BL/6 mice and of mice bearing the scid defect to determine where, when, and whether IL-2 is expressed in vivo. Our results show a striking spatial and temporal pattern of IL-2 expression in the normal fetal thymus. We detected a burst of IL-2 mRNA accumulation at day 14.5 of gestation, which rapidly decreased by day 15. At day 15, we observed maximal IL-2 protein production that subsequently decreased by day 16 of gestation. Both in situ hybridization and immunohistochemical staining revealed an unexpectedly strict localization of IL-2 expressing cells to patches around the periphery of the fetal thymus, creating a previously unrecognized compartment of high IL-2 protein content. IL-2 production in the day-15 fetal thymus appeared to be unaffected by the scid mutation, indicating that this response is likely to be T-cell receptor (TcR)-independent. Several features distinguish the IL-2 induction pattern in the adult thymus from that in the fetal thymus. In the normal adult thymus, IL-2-expressing cells are extremely rare (found at a frequency of 10^(-7)), but they are reproducibly detectable as isolated cells in the outer cortex and subcapsular region of the thymus. Unlike the fetal thymic IL-2 producers, the IL-2 producers in the adult thymus are completely eliminated in mice homozygous for the scid mutation. This suggests that the IL-2-expressing cells in the normal adult thymus are of a more mature phenotype than the immature, TcR-negative cells that accumulate in the scid adult thymus. Thus, our work demonstrates that two developmentally distinct types of cell interactions induce IL-2 expression in vivo: one, a broadly localized interaction in day 14-15 fetal thymus that is unaffected by the scid mutation; the other, a rare event that occurs asynchronously from late fetal through adult life, but which is completely eliminated by the scid defect. These results imply that significant differences exist between the physiological processing of thymocytes in the fetal and postnatal thymic microenvironments.

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Rothenberg, Ellen V.0000-0002-3901-347X
Additional Information: © 1993 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Received August 21, 1992; accepted November 23, 1992. We are very grateful to Lisa Scherer and Paul Boyer for their helpful comments on the manuscript; to John Snyder for help with Fig. 6; to Robin Condie for excellent care of the SCID mice; to David Anderson, Eric Davidson, Peter Dervan, and William Dreyer for allowing us access to critical instrumentation used in this project; and to Cathy Blagg, for expert help in typing the manuscript. This work was supported by NIH grant AI19752.
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Subject Keywords:Interleukin-2 (IL-2); interleukin-2 receptor (IL-2R); thymus; in situ hybridization; immunohistochemistry; severe combined immunodeficiency (scid); T-cell receptor (TcR)
PubMed Central ID:PMC2275923
Record Number:CaltechAUTHORS:20120308-115336061
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Official Citation:Julia A. Yang-Snyder and Ellen V. Rothenberg, “Developmental and Anatomical Patterns Of IL-2 Gene Expression in Vivo in The Murine Thymus,” Developmental Immunology, vol. 3, no. 2, pp. 85-102, 1993. doi:10.1155/1993/86096
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:29655
Deposited By: Jason Perez
Deposited On:13 Apr 2012 22:48
Last Modified:06 Feb 2017 20:47

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